Fungal infections, particularly those caused by yeasts, are associated with high morbidity and mortality. An increase in the prevalence of nosocomial fungal infections, especially bloodstream infections (BSI) attributed to Candida species, has contributed to an overall increase in the proportion of BSI caused by yeast (Wisplinghoff CID 2004).
The susceptibility of the various Candida species to available antifungal compounds is constantly being reexamined and results are widely published. The susceptibility of an isolate to a drug is often described in minimum inhibitory concentration units (MIC) which are often defined in terms of the species as a whole, though susceptibilities can vary widely between isolates of a given species. Measurement of MIC values requires isolation of an organism from a clinical sample followed by exposure of the organism to a drug and subsequent measurement of inhibition (reduction in growth). The US National Committee for Clinical Laboratory Standards (NCCLS) guidelines attempt to standardize these techniques and establish so called “breakpoints” differentiating resistant from non-resistant isolates. In general terms, species are described as resistant to a particular drug when a significant proportion of isolates tested have MIC values greater than the breakpoint, or when the recommended dosage of a drug is found to result in failure of treatment in a significant number of cases. Organisms which demonstrate intermediate susceptibilities are described as “susceptible, dose-de pendant”.
Though the susceptibility of a given species to a particular drug can be highly variable between isolates, and patient populations, the established susceptibility of a species is perceived as a good therapeutic guide. In fact, current guidelines from the Infectious Disease Society of America recommend selection of antifungal therapy based on species identification. Antifungal drugs are approved for, and directed towards the treatment of particular Candida species, however; identification to a species level is not commonly performed rapidly enough to inform initial therapeutic decisions. Treatment of patients with antifungal drugs is therefore often performed prophylactically, without diagnostic information, or empirically based on preliminary diagnostic information; whereas, selection of optimal therapy must await laboratory identification which may take several days by conventional methods.
Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, and Candida krusei account for greater than 95% of yeast isolates from blood (Pfaller JCM, Vol. 39, No. 9. p. 3254-3259) and greater than 97% of nosocomial fungal infections (Wisplinghoff CID 2004). A trend in the relative proportions of these high prevalence Candida species has shifted towards a higher incidence of the “drug resistant” species C. glabrata and C. krusei in some patient populations (Trick et al CID 1998). It has been suggested that this change in species proportion reflects a selection of resistant nosocomial strains through the over use of empiric antibiotics.
The development of antifungal therapy is focused on broad spectrum drugs to reduce the dependence on laboratory identification; however, broad spectrum antifungal drugs may be expensive or associated with adverse side effects. For the antifungal compound, fluconazole, the five most clinically prevalent Candida species are generally regarded to fall in three categories. C. albicans and C. parapsilosis are fluconazole sensitive, C. tropicalis has dose-dependent sensitivity to fluconazole, and C. glabrata with high prevalence of fluconazole resistance and C. krusei which is considered fluconazole resistant. Thus, it is generally accepted that infections of C. albicans or C. parapsilosis can be treated with a normal regime of fluconazole. Fungal infections caused by C. tropicalis can be treated with either an increased dose of fluconazole, or a stronger antifungal drug. C. glabrata and C. krusei infections are generally treated with caspofungin, voriconazole, amphotericin B, or other strong antifungal compounds.
It would therefore be advantageous to have laboratory tools where the results could be used to select optimal antifungal therapy without having to identify the yeast at the species level.